Synthetic α-hydroxytropolones as inhibitors of HIV reverse transcriptase ribonuclease H activity12. Issue 9 (18th July 2016)

• Record Type: Journal Article
• Authors: Murelli, Ryan P.; D'Erasmo, Michael P.; Hirsch, Danielle R.; Meck, Christine; Masaoka, Takashi; Wilson, Jennifer A.; Zhang, Baofeng; Pal, Rajat K.; Gallicchio, Emilio; Beutler, John A.; Le Grice, Stuart F. J.
• Is Part Of: MedChemComm. Volume 7:Issue 9(2016:Sep.)
• Page Start: 1783
• Page End: 1788
• Publication Date: 2016-07-18
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00238b
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : HIV reverse transcriptase-associated ribonuclease H activity is a promising enzymatic target for drug development. The following describes the activity of synthetic α-hydroxytropolones in HIV ribonuclease H-associated assays. Abstract : HIV reverse transcriptase-associated ribonuclease H activity is a promising enzymatic target for drug development that has not been successfully targeted in the clinic. While the α-hydroxytropolone-containing natural products β-thujaplicinol and manicol have emerged as some of the most potent leads described to date, structure–function studies have been limited to the natural products and semi-synthetic derivatives of manicol. Thus, a library of α-hydroxytropolones synthesized through a convenient oxidopyrylium cycloaddition/ring-opening sequence have been tested in in vitro and cell-based assays, and have been analyzed using computational support. These studies reveal new synthetic α-hydroxytropolones that, unlike the natural product leads they are derived from, demonstrate protective antiviral activity in cellular assays.